A total of 41 825 metal-organic frameworks (MOFs) were computationally screened toward the design of amine-functionalized MOFs for CO 2 separation. Both the optimal species and number of amine functional groups were examined for eight MOFs with good performance in terms of CO 2 uptake and selectivity. It was revealed that more amine functional groups grafted on the MOFs do not lead to a better CO 2 separation capability, and the concept of saturation degree of functional groups was proposed. The ethylenediamine-functionalized MOF-74 membrane was predicted to possess high CO 2 permeation separation capability, which was confirmed by the parallel experimental test of gas permeation.Metal-organic frameworks (MOFs) have received tremendous interest in the past few decades due to their large potential for H 2 storage, 1 CO 2 capture, 2 catalysis, 3 gas separation and purification, 4 liquid separation 5 and drug delivery. 6 However, the performance of many synthesized MOFs cannot satisfy industrial demands. Therefore, their functionalized counterparts have attracted considerable attention because they are more effective compared with the original ones, such as their higher separation efficiency, 7 gas storage, 8 catalytic performance 9 and luminescence capability. 10 H 2 and CH 4 are considered as environmentally friendly energy carriers and have received much attention. Nevertheless, the presence of CO 2 in them remarkably decreases their heat values. Moreover, in a moist environment, CO 2 can react with water to produce carbonic acid, leading to corrosive effects not only on the equipment but also on the pipes during transportation. 11 Consequently, CO 2 separation from H 2 or CH 4 is crucial in the processing of clean fuels. Toward this end, the functionalization of MOFs by amine functional groups has been recognized as an effective technique to improve the adsorption and separation of acidic CO 2 . 12 In the literature, a larger number of amine-functionalized MOFs have been synthesized and tested. 13 Vaidhyanathan et al. 14 reported the crystallographic resolution of amine-functionalized MOFs and their analysis showed that the low-pressure binding and large uptake of CO 2 were influenced by three factors, i.e., strongly interacting amine functional groups, suitable pore size and the cooperative binding of CO 2 molecules. Ahnfeldt et al. 15 synthesized four amine-functionalized MOFs including CAU-1-NH 2 , CAU-1-NHCH 3 , CAU-1-NH 2 (OH) and CAU-1-NHCOCH 3 , and examined the effects of time and temperature.While a wide variety of MOFs can be modified for CO 2 separation, it remains elusive which specific MOFs are suitable to be functionalized, which functional groups have the best improvement and what is the optimal number of functional groups. In most experimental efforts, many MOFs were modified by trial-and-error, resulting in a slight chance of successful synthesis and actual enhancement in performance. It is thus of great significance to unravel how functionalized MOFs can be rationally designed from a computa...